The term active substances in the present context is understood to mean substances having a desired action, of either an optical, physical or chemical/biological nature, in a field of technology, medicine or biology, including pest control.
The delivery of active substances therefrom to a specific acceptor medium can take place in two ways with respect to the time function.
On the one hand the total desired active substance quantity can be supplied in a single portion and on the other hand the desired total quantity can be supplied discontinuously or continuously, subdivided into partial quantities of varying magnitude, over a given period of time to the acceptor medium. The present invention deals with the latter case.
The present invention relates to the delivery of active substance from a reservoir to a specific acceptor medium. Apart from the controllability of the active substance quantity delivered in time and in the time unit by the reservoir, it must also be possible here to control the active substance delivery characteristics. This requirement is in many cases unavoidable and e.g. in the case of transdermal, therapeutic systems plays an important part. These are active substance-containing apparatuses or administration forms, which deliver to the skin over a fixed time period and in a continuous manner one or more active substances with a predetermined rate. Considerable efforts have been made to realize these systems.
The aim of obtaining an approximately constant active substance delivery over a desired period of time has been achieved. Solution proposals exist for other active substance delivery characteristics which have not, however, been fully satisfied. Thus, use must be made of the composition of the reservoir matrix in connection with a controlled decrease in the active substance delivery over the administration period (in the case of medicaments this decrease is e.g. sought in the case of cortisone-containing products, as well as in nitroglycerin administration, but may also be necessary for adapting to the biorhythm of the organism under treatment). However, this only offers a limited scope, because it is also necessary to fulfil the basic requirement of the diffusability of the active substance in the matrix. The concentration and/or concentration distribution of the active substance in the matrix also offer possibilities of control in the desired sense, but can only be used in special cases.
U.S. Pat. No.4,564,364 proposes subdividing the active substance reservoir into volume areas, in which the active substance concentration is partly above and partly below the saturation concentration. Through a planned geometrical design of the volume areas, it is possible to influence the active substance delivery characteristics. Quite apart from the fact that the production of such systems is complicated and costly, it does not disclose the present technical teaching of solving the problem of a planned, controlled decrease in the active substance delivery over the administration or application time of the system.
Another way for controlling the active substance delivery from matrix reservoirs is given in German Patent 33 15 272. In this case the reservoir comprises at least two layers parallel to the delivery surface, which contain concentrations above the saturation concentration, the concentration increasing with increasing distance of the layer from the delivery surface. This admittedly makes it possible to keep the delivery rate at a given level for this desired time, but here again it is not possible to achieve a planned control of the decrease in the active substance delivery rate. EP-A-0 227 252 describes an active substance delivery characteristic particularly in connection with transdermal therapeutic systems, in which with the aid of an enhancer, it is possible to set a high delivery rate over a first part of the administration period, with a much lower delivery rate over a second part of said period. The construction and composition of the reservoir are very complicated and must be determined for each individual case on the basis of time-consuming preliminary tests. In addition, this system is limited to a two-stage active substance delivery characteristic.